Synthesis of azulenyl-substituted gold(i)-carbene complexes and investigation of
their anticancer activity
#MMPMID41163828
Dietl MC
; Hüßler C
; Scherr M
; Frederiksen ZM
; Graf J
; Rominger F
; Rudolph M
; Caligiuri I
; Tripodi L
; Rizzolio F
; Scattolin T
; Hashmi ASK
RSC Adv
2025[Oct]; 15
(49
): 41260-41269
PMID41163828
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The direct and atom economic synthesis of azulenyl-substituted gold(i) carbene
complexes, based on the modular template synthesis using gold(i) isonitrile
complexes and amine nucleophiles, is presented. First, two azulenyl-substituted
isonitriles as ligands were synthesized from a functionalizable azulene
derivative, the latter stemming from a gold-catalyzed dimerization of internal
alkynes. These azulene-bound gold(i) isonitrile complexes allow the smooth
nucleophilic attack by both aliphatic and aromatic amines. The newly synthesized
azulene-substituted gold(i) carbene complexes were evaluated for in vitro
anticancer activity against multiple human cancer cell lines. Six lead compounds
demonstrated potent and selective cytotoxicity, exceeding that of cisplatin by at
least an order of magnitude in resistant and aggressive cancer models.
Structure-activity relationship analysis revealed that specific ligand
modifications, such as the position of the azulene moiety tethered to the carbene
unit or nitrogen-bound ethyl or cyclic groups, are critical for enhancing the
anticancer activity.
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